HEAT ACTIVATED MICROPARTICLE DRUG DELIVERY SYSTEMS

点击翻译按钮获取中文摘要

The overall objective of the project is to develop heat activated microparticle drug delivery systems for delivery of chemotherapeutic agents that could be used in conjunction with therapeutic hyperthermia or hyperthermia plus radiation. During Phase 1 microparticles will be prepared from Riboflavin and triglyceride esters of higher fatty acids which melt at a temperature of 40-45"C. Riboflavin was selected as a model compound because it is significantly less costly than antitumor agents. Microspheres (1-10 am) will be prepared by a solvent evaporation process which produces a monolithic drug polymer matrix. A new microfluidized bed process developed by BIOTEK will be used to produce true wall/reservoir microcapsules in which the drug is completely surrounded by a triglyceride ester wall material. Preliminary studies indicate that microparticles can be effectively coated with triglyceride esters. The microparticles will be evaluated in vitro release of the drug at incremental temperatures from 37degrees C to 45degrees C. In addition, they will be characterized as to drug content, size distribution, and surface morphology. The most promising formulation will be evaluated in vivo in mice. The Phase 1 studies will be provide the basis for further development of the process in Phase 11 and the microencapsulation of chemotherapeutic agents which would benefit from activation by therapeutic hyperthermia. The ultimate goal is to complete development, conduct necessary preclinical tests, prepare documentation for an IND, and to begin clinical studies by the completion of SBIR Phase 11.